An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor

Yoshikawa, Keiichi; Nakagawa, Hiroaki; Mori, Nozomu; Watanabe, Hidenobu; Touhara, Kazushige

doi:10.1038/nchembio.1164

Cited by 54 publications

(60 citation statements)

References 25 publications

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“…S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1)(2)(3)(4)(5)(6)(7)(8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9,10).…”

mentioning

confidence: 99%

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Matsuo¹,

Hattori

Asaba

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.social behavior | pheromone processing | main olfactory system | vomeronasal system M ost mammals have two major olfactory subsystems-the main olfactory system (MOS) and vomeronasal system (VNS). The MOS comprises the main olfactory epithelium (MOE), in which olfactory sensory neurons detect odorants, and their projection target, the main olfactory bulb (MOB) (Fig. S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1-8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9, 10). In mice, chemical ablation of the MOE impairs male and female sexual behaviors (11,12). In these experiments in which the MOE was ablated, the function of the VNS is not directly disrupted, because the VNS is activated by direct application of urine to the nostril. Thus, these results indicate that the MOS also contributes to pheromone processing and related behaviors.Nonconditional disruption of genes encoding signal transduction proteins that are required for activation of olfactory neurons, such as cyclic nucleotide-gated channel (Cnga2) or adenylyl cyclase 3, impairs several social behaviors (11,(13)(14)(15). However, complete loss of MOS function causes a...

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mentioning

confidence: 99%

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Matsuo¹,

Hattori

Asaba

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Ultimately, different odorants are represented as different combinations of activated ORs. Researchers have worked intensively for >15 yr to identify ligands for ORs (Krautwurst et al 1998;Touhara et al 1999;Yoshikawa et al 2013;Shirasu et al 2014). Saito et al (2009) performed the most comprehensive of these studies; in that study, they screened 93 odorants against 464 ORs and successfully deorphanized 10 human and 52 mouse ORs.…”

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confidence: 99%

Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals

2014

Self Cite

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Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species—reflecting the respective species' lifestyles—and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory.

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“…Even though some ORs apparently recognize a wide spectrum of odorants in laboratory experiments and could therefore be called broadly tuned receptors, only one naturally occurring ligand may exist for that OR and the structures of the natural ligand could be totally different from those of the synthetic ligands, and thus, the receptor should actually be categorized as a narrowly tuned receptor. Three examples of natural ligand-receptor pairs have been reported: Z5:14-OH-Olfr288 (Yoshikawa et al 2013), MTMT-MOR244-3 (Duan et al 2012), and OR37-C14-C18 aldehydes (Bautze et al 2012). Olfr288 appears to recognize a broad range of lactone compounds and aliphatic alcohols in laboratory experiments but is actually narrowly tuned to Z5:14-OH in a natural environment.…”

Section: Physiological Odorant Receptor Functionmentioning

confidence: 96%

“…For example, MTMT and Z5-14:OH, which are included in mature male urine, attract female mice, although Z5-14:OH requires other urinary compound(s) for the activity. One of the ORs for MTMT is MOR244-3 (Duan et al 2012), and the one for Z5-14:OH is Olfr288 (Yoshikawa et al 2013). There appear to be a few additional ORs for these compounds.…”

Section: From Receptor To Behaviormentioning

confidence: 99%

“…Recently, Yoshikawa et al developed a highly efficient OR assay with no background that can be used to purify natural ligands for ORs. For example, they used crude extracts, OR assay-guided fractionation, and chemical analysis to identify (Z)-5-tetradecen-1-ol, a putative fatty acid metabolite, as a natural ligand for Olfr288 in male urine that attracted females (Yoshikawa et al 2013). In another study, they identified natural ligands for OR37 and showed that these were also fatty acid derivatives, specifically C14-C18 aldehydes (Bautze et al 2012), although the functional proof in heterologous cells has not been provided.…”

Section: Vertebrate Odorant Receptorsmentioning

confidence: 99%

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Odor and Pheromone Molecules, Receptors, and Behavioral Responses

Touhara

2014

The Olfactory System

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Knowledge about chemosensory signals, receptors, olfactory neural network, and behavioral outputs has grown rapidly. Thus, the molecular logic that mediates recognition and discrimination of chemosensory signals has been revealed. Here, I first summarize the current understanding of mammalian olfaction, from the odorant or pheromone, to the receptor, and finally to the behavioral output. I then discuss important questions to be solved in the future and give some insights. Specifically, how should we categorize volatile compounds that are received by olfactory systems in animals? What should be the next focus of research in the field of olfactory receptors? How can we connect a receptor response to a cognate, biologically meaningful odorant or pheromone with the respective behavioral or physiological output at the level of neural circuitry?

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An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor

Cited by 54 publications

References 25 publications

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals

Odor and Pheromone Molecules, Receptors, and Behavioral Responses

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